Drugs For Parkinson's

Drugs for Parkinsonism and Parkinson’s Disease
I. Parkinsonism
• group of disorders that share four main symptoms:
1. tremors
2. rigidity
3. slowness of movement (bradykinesia)
4. poor balance and coordination.
Idiopathic Parkinson’s Disease

• loss of dopamine- secreting neurons in substantia nigra
• cause unknown (idiopathic)
• causal theories:
 viral infection
 head trauma
 atherosclerosis
Pseudoparkinsonism/ Drug –induced Parkinsonism

• causes:
 antipsychotics (phenothiazines)
 poisons (carbon monoxide, manganese)
Basal ganglia cells
INHIBITION STIMULATION
Type 1 drugs Type 2 drugs

Dopaminergics Anticholinergics
A. Dopaminergics
A. biperiden (Akineton)
• Levodopa* B. benztropine(Cogentin)
• Carbidopa- levodopa (Sinemet) C. diphenhydramine
(Benadryl)
D. procyclidine
B. MAO –B inhibitor
• Selegiline E. trihexyphenidyl
(Artane)
C. COMT inhibitors
• tolcapone
• entacapone
D. Dopamine Agonists
• amantadine pramipexole
• ropinirole pergolide
• bromocriptine
A. Dopaminergics
MOA: increase dopamine concentration
1. Levodopa
Indic: DOC for idiopathic parkinson’s dse
SE/ adverse effect:: (high dose)

• N&V
• dyskinesia
• psychosis
• Increase libido
• orthostatic hypotension, cardiac dysrhythmias
 assoc. melanoma formation

 “ on – off” fluctuations
2. Carbidopa – Levodopa (Sinemet)

• Advantages:
• more dopamine reaches basal ganglia
• smaller dose of dopamine required
• single dosaging
Indic: Idiopathic parkinson’s dse
SE:
• more severe -in high doses
B. Dopamine agonists
1. Amantadine (Symmetrel)
MOA: increases dopamine release
Indic:
1. early onset idiopathic parkinson’s disease
2. early onset drug- induced parkinsonism
3. influenza A respiratory virus
2. Bromocriptine (Parlodel)
Pergolide
Pramipexole
Ropinirole
MOA: stimulate dopamine receptors
S/E of Dopaminergics & dopamine agonists:
1. dyskinesia
2. involuntary body movements
3. tachycardia
4. N&V
5. urinary retention
6. constipation
7. dizziness & orthostatic hypotension
8. psychosis
 Contraindications to dopaminergics & dopamine agonists:

1. narrow angle glaucoma
2. suspicious skin lesions
3. lactation
4. severe cardiac dse
5. severe renal problem
6. severe psychiatric problem
 Drug interactions:
• pyridoxine (Vit B6 ) decrease effect of levodopa
• antipsychotic drugs
• phenytoin
• MAO inhibitors & TCA ---> hypertensive crisis if taken with levodopa
C. MAO - B inhibitor
 selegiline
MOA: inhibits monoamine oxidase (MAO) –B ---> prolongs action of levodopa
Indic:
1. early onset parkinsonism
2. decrease “on –off” fluctuation of levodopa
SE;
Dopaminergics/ Dopa agonists + MAOI --> hypertensive crisis
Tyramine + MAOI
D. COMT inhibitors
MOA: inhibit COMT ---> incease levodopa concentration in brain
1.Tolcapone
2.Entacapone
Indication:
1. adjunct to levodopa / sinemet therapry
SE;
• severe liver damage
• dark yellow to orange urine
E. Anticholinergics
MOA: block stimulating effects of Ach --> reduce tremors & rigidity,
minimal effect on bradykinesia
1. Benztropine (Cogentin)
2. Biperiden (Akineton)
3. Trihexyphenidyl (Artane)
Indic:
1. drug –induced parkinsonism
2. Parkinson’s disease
SE: same as Atropine

• BLOCK SLUDS
• disorientation & confusion, memory loss
• hypotension, tachycardia
Drug interactions:
• phenothiazines, antihistamines, TCA ---> increasese anticholinergic properties
• Antipsychotics --> decrease effect of anticholinergics
CI:
• Narrow- angle glaucoma
• Intestinal & urinary obstruction
• BPH
• Myasthenia gravis
• COPD
• Severe memory loss/dementia
Patient: Doctor, I have a split personality.
Psychiatrist: Nurse, bring in another chair.

Drugs for Myasthenia Gravis
Myasthenia Gravis
• autoimmune disease
• lack of acetylcholine (Ach) reaching cholinergic receptors in skeletal muscle
• s/sx:
o ptosis & diplopia
o weaknes & fatigue of skeletal muscles
o dysphagia
o dysarthria
o respiratory muscle weakness
Drug Therapy:
A. Acetylchoinesterase Inhibitors/ Cholinesterase Inhibitors (AChE inhibitors)

MOA: inhibit cholinesterase --> more Ach activates cholinergic receptors ---> promote
muscle contraction
1. Ultra-shorting
 Edrophonium (Tensilon)
 Myasthenia Crisis vs Cholinergic crisis
Sx: muscle weakness muscle weakness

Cause: : underdose of AChE inhibitors overdose of AChE inhibitors
Tensilon test : positive negative
Tx : pyridostigmine atropine sulfate
2. Short- acting
• Neostigmine (Prostigmin)
3. Intermediate- acting
• Pyridostigmine (Mestinon)*
4. Long- acting
• Ambenonium
SE;
• INCREASE SLUDS
• hypertension
B. Glucocorticoid
 Prednisone
Indic: decreases MG sxs & promotes remission
SE: increase blood sugar, abnormal fat deposits, muscle wasting

C. Immunosuppressive agent
 Azathioprine (imuran)
SE: leucopenia, hepatotoxicity
Drugs for Mutiple Sclerosis
Multiple Sclerosis
 autoimmune disease
 attacks myelin sheath of nerves in brain & spinal cord
 s/sx:
• diplopia
• weakness in extremities
• spasticity of extremities
Drug therapy:
Phase of MS S/Sxs Treatment
1. Acute Attack: fatigue, optic neuritis prednisone

motor weakness ACTH
2. Remission-exacerbation
recurrence of MS sxs betaseron - interferon- beta
spasticity azathioprine immunosuppressants
cyclophosphamide
3. Chronic Progressive
progressive MS sxs cyclophosphamide (Cytoxan)
(wheel-chair bound) ACTH
Drugs to avoid in MS:

1. antihistamine / histamine (H2) blockers – ranitidine, cimetidine
2. NSAID - indomethacin
3. beta blocker - propanolol
Drugs for Alzheimer’s Disease
Alzheimer’s disease
 chronic, progressive neural degeneration in cortex
 s/sx;
o confusion
o marked memory loss ---> dementia
o Loss of judgement & time disorientation
o Inability to perform ADL
 cause unknown
 causal theories:
o progressive loss of Ach-producing neurons & deficiency in Ach
o neuritic plaques
o apolipoprotein E4 (apo E4)
o beta- amyloid protein
o neurofibrillary tangles inside neurons
Stage 1 Mild (early confusion) early cognitive decline

• memory loss
• recall difficulties
• some decrease in social functioning
Stage 2 Moderate unable to perform complex tasks

unable to concentrate
no knowledge of current events
stage 3 Moderately severe needs assistance for survival

(Early dementia) disoriented to time & events
stage 4 Severe needs assistance for survival

forget spouse & family members
unaware of surroundings
fecal & urinary incontinence
increase CNS disturbances
stage 5 Very severe limited speech, scream

(Late dementia) unable to ambulate, sit up or feed self
May slip into stupor / coma
Drug therapy:
A. Acetylcholinesterase (AChE) inhibitors / Cholinesterase (ChE) inhibitors
MOA: block Ache ----> allow more Ach to stimulate cholinergic receptors
 Tacrine (Cognex)*
 Donezepil (Aricept)
 Rivastigmine (Exelon)
 Memantine
SE/adverse effects: (increase SLUDS)

• Increase GI activity & secretions
• cardiodepression
• miosis, BOV
• dizziness & drowsiness
• weight loss
Drug interactions:
NSAIDS – increase GI secretions
Theophylline – increased 2x with tacrine
B. Investigational drugs for alzheimer’s:

 NSAIDS
 Calcium blockers
 MAO- B inhibitors
 ACE inhbiibitors
Until you value yourself, you won't value your time.

Until you value your time, you will not do anything with it.
M. Scott Peck

Drugs For Parkinson's

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Drugs for Parkinsonism and Parkinson’s Disease

Idiopathic Parkinson’s Disease

Pseudoparkinsonism/ Drug –induced Parkinsonism

Basal ganglia cells

Type 1 drugs Type 2 drugs

Indic: DOC for idiopathic parkinson’s dse

SE/ adverse effect:: (high dose)

 assoc. melanoma formation

2. Carbidopa – Levodopa (Sinemet)

Indic: Idiopathic parkinson’s dse

 Contraindications to dopaminergics & dopamine agonists:

SE: same as Atropine

Patient: Doctor, I have a split personality.

Psychiatrist: Nurse, bring in another chair.

A. Acetylchoinesterase Inhibitors/ Cholinesterase Inhibitors (AChE inhibitors)

 Myasthenia Crisis vs Cholinergic crisis

Sx: muscle weakness muscle weakness

SE: increase blood sugar, abnormal fat deposits, muscle wasting

Drugs for Mutiple Sclerosis

Phase of MS S/Sxs Treatment

1. Acute Attack: fatigue, optic neuritis prednisone

Drugs to avoid in MS:

Stage 1 Mild (early confusion) early cognitive decline

Stage 2 Moderate unable to perform complex tasks

stage 3 Moderately severe needs assistance for survival

stage 4 Severe needs assistance for survival

stage 5 Very severe limited speech, scream

A. Acetylcholinesterase (AChE) inhibitors / Cholinesterase (ChE) inhibitors

SE/adverse effects: (increase SLUDS)

B. Investigational drugs for alzheimer’s:

Until you value yourself, you won't value your time.

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